BH<sub>3</sub>-Promoted Stereoselective β-Lithiation of <i>N</i>-Alkyl-2-phenylaziridines

Azzena, Ugo; Dettori, Giovanna; Pisano, Luisa; Musio, Biagia; Luisi, Renzo

doi:10.1021/jo102474u

Cited by 22 publications

(16 citation statements)

References 33 publications

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“…It has been reported previously that the aziridino group acts as an ortho-directing group in N-alkyl-2-phenylaziridines. Nevertheless, the corresponding BH 3 complex is regioselectively lithiated at the β-cis position with respect to the phenyl ring, and the lithiated intermediate is configurationally stable allowing also an enantioselective preparation of cis-2,3-disubstituted aziridines (Scheme 7.13) [18]. A similar reactivity has been observed for other N-alkyl aziridine-borane complexes by Edwin Vedejs and Concellón [19].…”

Section: Three-membered Rings: Lithiated Aziridinessupporting

confidence: 59%

Nitrogen‐Bearing Lithium Compounds in Modern Synthesis

Degennaro¹,

Musio²,

Luisi³

2014

Lithium Compounds in Organic Synthesis

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IntroductionNitrogen-containing compounds are ubiquitous and are extremely important in synthesis. This chapter reports some general aspects of the generation, structure, and reactivity of nitrogen-bearing organolithiums showing the progress made over the last decade. The chapter does not cover comprehensively the field but the aim is to provide the reader with useful information on the generation, reactivity, and potential in synthesis of this kind of lithiated intermediates.Throughout the chapter, the name amino-organolithiums is used to describe reactive intermediates lithiated at sp 3 -hybridized carbon atoms adjacent (α) to a nitrogen atom that could be included also in a ring. Amino-organolithiums can be generated mainly in three different ways: (i) deprotonation of a parent amine or its derivative; (ii) transmetallation by using an alkyllithium; and (iii) reductive cleavage of C-heteroatom bond (e.g., C-S). Each way has advantages and disadvantages and in some cases they complement each other (Scheme 7.1).Direct deprotonation is a widely used strategy to generate amino-organolithiums even in chiral form, while tin-lithium exchange reactions are preferred when direct deprotonations are difficult (high kinetic barrier) or regiochemical issues apply. Concerning the direct deprotonation of amines, this is not a simple task because the corresponding lithiated intermediates suffer from destabilizing interactions that make this reaction very difficult unless a ''stabilizing group'' (SG) is introduced either on the nitrogen atom or on the lithium-bearing carbon (Scheme 7.2).The SG (Scheme 7.2) has a pivotal role, either reducing the kinetic barrier in the hydrogen/lithium permutation or stabilizing the organolithium mesomerically or by coordination. For these reasons, often, amino-organolithiums are classified as stabilized or unstabilized. The chemistry of unstabilized amino-organolithiums has been so far less developed however, lithiation of simple tertiary amines could be accomplished by two main strategies: (i) by tin/lithium exchange reaction and (ii) by deprotonation of quaternary ammonium complexes (Scheme 7.3).

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Section: Three-membered Rings: Lithiated Aziridinessupporting

confidence: 59%

Nitrogen‐Bearing Lithium Compounds in Modern Synthesis

Degennaro¹,

Musio²,

Luisi³

2014

Lithium Compounds in Organic Synthesis

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“…[57] A preliminary BH 3 complexation of terminal N-alkyl-2-phenylaziridines to give the Lewis adduct 96 makes possible a regioselective β-lithiation. [58] The resulting lithiated intermediates 96 proved to be configurationally stable, allowing an enantioselective preparation of cis-2,3-disubstituted aziridines 98 by removal of the BH 3 group of 97. The structure and stereochemistry of the synwww.eurjoc.org The versatility of the lithiation reaction of aziridines proved to be remarkable.…”

Section: α-Vs Ortho-lithiation Of Arylaziridinesmentioning

confidence: 99%

Complexation Phenomena and Dynamics at Work in the Lithiation Reactions of Small‐Ring Heterocycles: Regio‐ and Stereoselectivity

2014

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This Microreview focuses on the regio- and stereoselective lithiation of small-ring heterocycles such as aryl-substituted oxiranes, aziridines, azetidines, oxetanes, and tetrahydrofurans highlighting some useful selected synthetic applications extracted from recent literature. It will be shown, in particular, that regio- and stereoselectivity and the configurational stability of the above lithiated species are controlled by a subtle interplay of factors. Aggregation, complexation phenomena, dynamics at the heteroatom of the heterocyclic ring, substitution in both the aryl and the heterocyclic ring, solvent polarity, temperature, and ligands play a crucial role. The ability of the afore-mentioned heterocycles as important directed metalation groups for the arene ortho-functionalization is also discussed as well as the carbene-like nature exhibited by some lithiated epoxides and aziridines. This Microreview focuses on the regio- and stereoselective preparation of α- and ortho-lithiated oxiranes, aziridines, oxetanes, azetidines, and tetrahydrofurans with special emphasis on factors such as carbene-like character, aggregation, complexation phenomena and dynamics which strongly influence their applications to synthetic chemistry. Recent selected examples extracted from the literature are critically analysed and commented

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“…Some of the systems that have been successfully investigated are reported in Scheme and include aziridines, azetidines and thietanes. In the case of diastereomeric aziridino–borane complexes 1a and 1b , we demonstrated their stereochemistry on the basis of proton NMR calculations . More recently, slowly equilibrating invertomers 2a and 2b were computationally investigated in order to explain the stereochemical course of the metalation reaction.…”

Section: Introductionmentioning

confidence: 99%

Computational NMR as Useful Tool for Predicting Structure and Stereochemistry of Four‐Membered Sulfur Heterocycles

Pisano¹,

Degennaro

Carraro³

et al. 2016

Eur J Org Chem

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We report a computational NMR study of stereochemically challenging thietane 1-oxides. Comparison of calculated and experimental data allows to assign structure and stereochemistry to the examined molecules. Computations included full conformational analysis of each thietane, DFT geometry optimizations and GIAO NMR calculations. Among the possible stereoisomers, only the computed structures with the correct stereochemistry were found to fit experimental NMR spectroscopic data. Computational analysis provide useful information on the conformational ring preference not easy to disclose by conventional structural analysis

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BH₃-Promoted Stereoselective β-Lithiation of N-Alkyl-2-phenylaziridines

Cited by 22 publications

References 33 publications

Nitrogen‐Bearing Lithium Compounds in Modern Synthesis

Nitrogen‐Bearing Lithium Compounds in Modern Synthesis

Complexation Phenomena and Dynamics at Work in the Lithiation Reactions of Small‐Ring Heterocycles: Regio‐ and Stereoselectivity

Computational NMR as Useful Tool for Predicting Structure and Stereochemistry of Four‐Membered Sulfur Heterocycles

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BH3-Promoted Stereoselective β-Lithiation of N-Alkyl-2-phenylaziridines

Cited by 22 publications

References 33 publications

Nitrogen‐Bearing Lithium Compounds in Modern Synthesis

Nitrogen‐Bearing Lithium Compounds in Modern Synthesis

Complexation Phenomena and Dynamics at Work in the Lithiation Reactions of Small‐Ring Heterocycles: Regio‐ and Stereoselectivity

Computational NMR as Useful Tool for Predicting Structure and Stereochemistry of Four‐Membered Sulfur Heterocycles

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BH₃-Promoted Stereoselective β-Lithiation of N-Alkyl-2-phenylaziridines